Before and after treatment with methylprednisolone-pulse therapy (MPT), we investigated the superoxide production from the neutrophils of 10 patients stimulated by phorbol myristate acetate, N-formyl-methionyl-leucyl-phenylalanine or opsonized zymosan. Effects of pre-treatment with patient serum on neutrophils from control subjects were also examined. Patient neutrophils produced significantly less superoxide after MPT than before MPT. The superoxide production was significantly less in normal neutrophils from control subjects pre-treated with patient serum after MPT than in those before MPT. Neutrophils pre-treated with control serum-supplemented with or without methylprednisolone secreted essentially the same amount of superoxide. These findings indicate that MPT suppresses superoxide production by neutrophils, which is not a direct effect of methylprednisolone on neutrophils. We assume that MPT may reduce some factors from lymphocytes which stimulate not only neutrophils but also macrophages producing superoxide. This effect on the macrophages which present in the pathologic lesion may be the origin of medicinal effects of MPT.